The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic Treg Cell Homeostasis

PM Smith, MR Howitt, N Panikov, M Michaud… - Science, 2013 - science.org
PM Smith, MR Howitt, N Panikov, M Michaud, CA Gallini, M Bohlooly-y, JN Glickman…
Science, 2013science.org
Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for
regulating intestinal inflammation. Candidate microbe approaches have identified bacterial
species and strain-specific molecules that can affect intestinal immune responses, including
species that modulate Treg responses. Because neither all humans nor mice harbor the
same bacterial strains, we posited that more prevalent factors exist that regulate the number
and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota …
Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota–derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
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